Biology subjects

Willems, T.

Publications and source records attributed to Willems, T..

3 recordsLinked to original sources

bioRxiv2025

Neural Traces of Forgotten Memories Persist in Humans and are Behaviorally Relevant

For a long time, forgetting has been taken as the dissipation of the neural memory traces (engrams). However, recent engram research in mice suggests that the engrams of forgotten memories do persist. This raises the question of whether engrams underlying human episodic memories also persist despite forgetting? And do forgotten memories influence human behavior implicitly? To address these questions, we used high-resolution functional magnetic resonance imaging at 7 Tesla to map the fate of 96 associative memories at the systems level from learning to a 30-minute and onward to a 24-hour memory test. Upon each retrieval attempt, participants indicated whether they remembered or forgot the memory. Univariate and multivariate analyses of the functional brain data revealed that the engrams of forgotten memories remain implemented in the episodic memory network and continue to influence the accuracy of guessing responses at the memory test. Overnight, the engrams of forgotten memories became implemented more deeply within bilateral hippocampus, while consciously accessible memories were neocorticalized overnight. The engrams of both consciously accessible and inaccessible (forgotten) memories shifted from the 30-minute to the 24-hour memory test within the right hippocampus and anterior cingulate gyrus as evidenced by the occurrence of pattern dissimilarities that supported correct retrieval responses at 24 hours. Hence, forgotten human episodic memories remain implemented in the episodic memory system and continue to influence decisions.

neuroscience↗

bioRxiv2020

A neural mechanism of social responsibility

This study investigated the neural mechanisms involved in feelings of interpersonal guilt and responsibility evoked by social decisions. In two studies (one during fMRI), participants repeatedly chose between safe and risky monetary outcomes in social contexts. Across conditions, each participant chose for both themselves and a partner (Social condition), or the partner chose for both themselves and the participant (Partner condition), or the participant chose just for themselves (Solo condition, control). If the risky option was chosen in the Social or Partner condition, participant and partner could each receive either the high or the low outcome of a lottery with 50% probability, independently of each other. Participants were shown the outcomes for themselves and for their partner on each trial, and reported their momentary happiness every few trials. As expected, participant happiness decreased following both low lottery outcomes for themselves and for the partner. Crucially, happiness decreases following low outcomes for the partner were larger when the participant rather than their partner had made the choice, which fits an operational definition of guilt. This guilt effect was associated with BOLD signal increase in the left anterior insula. Connectivity between this region and the right inferior frontal gyrus varied depending on choice and experimental condition, suggesting that this part of prefrontal cortex is sensitive to guilt-related information during social choices. Variations in happiness were well explained by computational models based on participants and partners rewards and reward prediction errors. A model-based analysis revealed a left superior temporal sulcus cluster that tracked partner reward prediction errors that followed participant choices. Our findings identify neural mechanisms of guilt and social responsibility during social decisions under risk.

neuroscience↗

bioRxiv2016

A framework to interpret short tandem repeat variation in humans

Identifying regions of the genome that are depleted of mutations can reveal potentially deleterious variants. Short tandem repeats (STRs), also known as microsatellites, are among the largest contributors of de novo mutations in humans and are implicated in a variety of human disorders. However, because of the challenges STRs pose to bioinformatics tools, per-locus studies of STR mutations have been limited to highly ascertained panels of several dozen loci. Here, we harnessed bioinformatics tools and a novel analytical framework to estimate mutation parameters for each STR in the human genome by correlating STR genotypes with local sequence heterozygosity. We applied our method to obtain robust estimates of the impact of local sequence features on mutation parameters and used this to create a framework for measuring constraint at STRs by comparing observed vs. expected mutation rates. Constraint scores identified known pathogenic variants with early onset effects. Our constraint metrics will provide a valuable tool for prioritizing pathogenic STRs in medical genetics studies.

genetics↗